We have isolated an angiogenic factor from human plasma and determined its probable three-dimensional structure in aqueous solution. This factor, Gly-His-Lys-copper(II) (GHL-Cu) induces new capillary growth in vivo while in vitro it alters the growth rate or state of differentiation of numerous cell lines. GHL-Cu is a chemotactic factor for endothelial and mast cells and may induce angiogenesis by accumulating these cells in localized areas. GHL binds copper to form a near planar, tridentate, triaza complex. Structural analogs of the GHL-Cu binding regions have been found to be potent inhibitors of DNA synthesis. One of these analogs, 2-pyridine-carboxaldehyde2'-pyridylhydrazone-copper(II) possesses substantial antineoplastic activity when tested against an implanted mouse fibrosarcoma. This research may clarify the mechanisms of tumor-induced angiogenesis and provide a basis for the synthesis of a new class of antineoplastic drugs.